Comparative Safety of Weight-Based versus Fixed-Dose Anticoagulation in Antiphospholipid Syndrome

Terezia Fabry; K. Ilavsky; D. Chudik

doi:10.5281/zenodo.22818754

Authors

Terezia Fabry Department of Transfusion Medicine and Blood Banking, Guadiana Institute of Hematologic Oncology Author https://orcid.org/4632-3124-8030-090X
K. Ilavsky Department of Coagulation Medicine, Volga Institute of Clinical Hematology Author https://orcid.org/3827-8792-2349-3866
D. Chudik Department of Laboratory Hematology, Maas Institute of Myeloproliferative Disease Research Author https://orcid.org/8949-9688-2317-2823

DOI:

https://doi.org/10.5281/zenodo.22818754

Keywords:

antiphospholipid syndrome, anticoagulation, warfarin, direct oral anticoagulants, thrombosis recurrence

Abstract

Graphical abstract

Background: Antiphospholipid syndrome (APS) confers a high risk of recurrent thrombosis, and secondary prevention has relied on INR-titrated vitamin K antagonist (VKA) therapy, which implicitly absorbs body-weight variability through its monitored endpoint.

Objective: To synthesize evidence on anticoagulation intensity, direct oral anticoagulant (DOAC) performance, and weight-based versus fixed-dose strategies for long-term anticoagulation in APS.

Methods: Narrative review of randomized trials of warfarin intensity, randomized DOAC-versus-warfarin trials in thrombotic APS, a patient-level meta-analysis of DOAC failures, and weight-based dosing evidence from other thrombotic indications.

Findings: Trials show no benefit of high-intensity over moderate-intensity warfarin in standard-risk APS, while fixed-dose rivaroxaban produced an unacceptable excess of arterial thrombosis (12% versus 0%) in triple-positive patients in TRAPS, replicated in an independent trial and a meta-analysis showing roughly sixfold higher recurrence odds with DOACs in triple-positive disease.

Conclusions: Monitored, INR-titrated VKA therapy remains the safest strategy for triple-positive thrombotic APS, and extrapolation from the thrombosis literature supports weight-conscious dosing at the extremes of body weight.

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